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Biomedical subjects

A Mayer

Publications and source records attributed to A Mayer.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Radiotherapy at the turn of the millennium].

The radiotherapy of the turn of the millenium has arisen as a result of continuous technical development, having taken place during the past 100 years. In the first 60 years it was, above all, a development of apperatures in the field of mechanics and radiophysics, originating a succession of different generations of megavolttherapy from the orthovolt one, radium being substituted in brachytherapy by surrogating nuclides. The motives for the development in the last 40 years have been microelectronics, computer technology and informatics. Owing to them, it became possible the digitalization of CT scans and CT assisted 3 dimension radiotherapy planningsystem. At the turn of the millenium, megavolttherapy and brachytherapy can only be remoted if computerized and perhaps with record and verify system a built-in on-line with portal imaging. In radiotherapy, technical development can motivate better therapeutic results only if treatments are given on tumorbiological-radiobiological basis which can essentially determine the totaldose and fractiondoses of radiotherapy and the total time and volume of radiation. A further task for radiotherapy is to examine how tumorregression can be influenced by alterated fractionation, by hyperthermia, by the oxigenization of the target volume eventually by chemotherapy and radioprotection of sourranding tissues.

Apoptosis↗
PubMed1999

Control of the terminal step of intracellular membrane fusion by protein phosphatase 1.

Intracellular membrane fusion is crucial for the biogenesis and maintenance of cellular compartments, for vesicular traffic between them, and for exo- and endocytosis. Parts of the molecular machinery underlying this process have been identified, but most of these components operate in mutual recognition of the membranes. Here it is shown that protein phosphatase 1 (PP1) is essential for bilayer mixing, the last step of membrane fusion. PP1 was also identified in a complex that contained calmodulin, the second known factor implicated in the regulation of bilayer mixing. The PP1-calmodulin complex was required at multiple sites of intracellular trafficking; hence, PP1 may be a general factor controlling membrane bilayer mixing.

Biological Transport↗
PubMed1999

Gene therapy--phase I trial for primary untreated head and neck squamous cell cancer (HNSCC) UICC stage II-IV with a single intratumoral injection of hIL-2 plasmids formulated in DOTMA/Chol.

Recombinant IL-2 protein has shown many immunostimulatory effects in a variety of human tumors. However, the clinical use of rIL-2 is limited by common and serious side effects after systemic administration. IL-2 expression plasmids may circumvent these drawbacks, producing high local IL-2 concentrations that cause limited or no systemic side effects. Due to the superficial growth of squamous cell carcinoma of the head and neck (HNSCC) are readily accessible for direct intratumoral injection and therefore an optimal target for such a gene therapy approach. There has been evidence for local and systemic activation of immune cells by peritumoral injections of IL-2 in patients with advanced HNSCC (Whiteside et al. 1993; Cortesina et al. 1994; De Stefani et al. 1996). We now perform a placebo-controlled, dose-rising study of the safety and tolerability of a single intratumoral injection of hIL-2 plasmid at four dose levels formulated in DOTMA/Chol in patients with primary untreated head and neck squamous cell cancer (HNSCC) TNM stage II-IV. The patients will be monitored for the occurrence of any adverse reactions to the given medication. In addition, we will determine whether the intratumoral administration of the plasmid induces and or enhances tumor-specific host responses at the immunological and or clinical level.

Carcinoma, Squamous Cell↗
PubMed1999

Unusual manifestation of an osteoid osteoma of the capitate.

A case of osteoid osteoma of the capitate in a 29-year-old male is reported. The patient suffered from unspecific clinical findings and a 3-year history of uncharacteristic wrist pain. Conventional radiographs of the wrist revealed a circumscribed sclerosis in the proximal part of the capitate bone beside a diffuse demineralisation of the carpal bones. Magnetic resonance imaging demonstrated a circumscribed, tumorous lesion with marked enhancement after IV administration of contrast agent and a highly calcified nidus, which was sharply demarcated by a small rim of granulation tissue from the surrounding spongious bone. Based on MRI findings, the diagnosis of an osteoid osteoma was established and confirmed after operation and histologic analysis.

Adult↗
PubMed1999

High performance medical image processing in client/server-environments.

As 3D scanning devices like computer tomography (CT) or magnetic resonance imaging (MRI) become more widespread, there is also an increasing need for powerful computers that can handle the enormous amounts of data with acceptable response times. We describe an approach to parallelize some of the more frequently used image processing operators on distributed memory architectures. It is desirable to make such specialized machines accessible on a network, in order to save costs by sharing resources. We present a client/server approach that is specifically tailored to the interactive work with volume data. Our image processing server implements a volume visualization method that allows the user to assess the segmentation of anatomical structures. We can enhance the presentation by combining the volume visualizations on a viewing station with additional graphical elements, which can be manipulated in real-time. The methods presented were verified on two applications for different domains.

Algorithms↗
PubMed1999

Intracellular membrane fusion: SNAREs only?

The past two years have seen vigorous attempts to elucidate the mechanism driving intracellular membrane fusion. Much attention was focused on the role of SNARE complexes. Their crystal structure was solved and fusion was reconstituted using proteoliposomes with purified SNAREs suggesting them to be the minimal machinery for fusion. Work on physiological membranes, however, points in another direction and has spurred a hot debate on the function of SNAREs.

Animals↗
PubMed1999

Mapping of semantic, phonological, and orthographic verbal working memory in normal adults with functional magnetic resonance imaging.

Twelve neurologically normal participants (4 men and 8 women) performed semantic, phonological, and orthographic working memory tasks and a control task during functional magnetic resonance imaging. Divergent regions of the posterior left hemisphere used for decoding and storage of information emerged in each working memory versus control task comparison. These regions were consistent with previous literature on processing mechanisms for semantic, phonological, and orthographic information. Further, working memory versus control task differences extended into the left frontal lobe, including premotor cortex, and even into subcortical structures. Findings were consistent with R. C. Martin and C. Romani's (1994) contention that different forms of verbal working memory exist and further suggest that a reconceptualization of premotor cortex functions is needed.

Adolescent↗
PubMed1999

An audit of breast cancer pathology reporting in Australia in 1995.

To measure the quality of pathology reporting of breast cancer and establish a baseline against which future changes can be measured, we audited item completeness in breast cancer reports in Australia in 1995 before the release of specific recommendations from the Australian Cancer Network. Tumour type and size were given in reports of invasive breast cancer for 93% of women, 70% had, in addition, grade and clearance of the margins while only 28% had all recommended information. The most complete items in reports were histological type of breast cancer (99.6% of cases), tumour size (94%, 95% confidence interval (CI) 92-95) and margins of excision (87%, 95% CI 85-89). Histological grade (84%, 95% CI 82-86 of cases) and presence or absence of ductal carcinoma in situ (DCIS) (79%, 95% CI 77-81) were less complete and vessel invasion (61%, 95% CI 58-63) and changes in non-neoplastic breast tissue adjacent to the breast cancer (68%, 95% CI 66-71) the least complete. Less than half the reports of DCIS reported on tumour size (49%, 95% CI 42-57), presence or absence of necrosis (41%, 95% CI 34-49) or nuclear grade (39%, 95% CI 31-46). Around 1500 reports were identified as issued by 147 laboratories and 392 pathologists; 69% of pathologists issued fewer than two reports a month in the audit. We concluded that infrequency of reporting may have contributed to incompleteness of reporting. In addition, we found significant variation across Australian states with some indication that reporting was consistently poor in one state. The audit highlighted areas for improvement for breast cancer reporting in Australia. Research evidence suggests that multifaceted strategies are needed to assist practitioners with implementing more uniform reporting standards.

Aged↗
PubMed1999

T cell response pattern to glutamic acid decarboxylase 65 (GAD65) peptides of newly diagnosed type 1 diabetic patients sharing susceptible HLA haplotypes.

Autoantibodies and autoreactive T lymphocytes directed against several pancreatic beta cell proteins such as GAD65 have been identified in the circulation before and at the onset of clinical type 1 (insulin-dependent) diabetes. Using GAD65 synthetic peptides, we studied the proliferative response of peripheral blood mononuclear cells (PBMC) either from recently diagnosed type 1 diabetic patients, of whom the majority share the disease-associated HLA class II haplotype (DR4-DQB1*0201 or DR3-DQB1*0302), or from HLA-matched control subjects. We found that 67% (14/21) of the type 1 diabetic patients and 39% (9/23) of the control subjects exhibited a positive proliferative response. Compared with control subjects, however, PBMC from diabetic patients proliferated more frequently (P < 0.05) in the presence of peptide pools from the C-terminal region of GAD65 (amino acids 379-585). Diabetic patients with the same HLA-DQ or HLA-DR alleles showed partially identical T cell reactivity, but no clear correlation could be made between MHC class II specificity and T cell epitopes because of multiple combinations of class II alleles. In addition, by flow cytometry, we studied the direct binding of GAD65 peptides to MHC class II molecules of Epstein-Barr virus (EBV)-transformed B (EBV-B) cells obtained from a diabetic patient. We found that 11 GAD peptides were able to bind to the highly susceptible haplotype DRB1*0301/0401-DQA1*0301/0501-DQB1*0302/0201 on the surface of EBV-B cells in partial correlation with the results obtained in the proliferation assays.

Adolescent↗
PubMed1999

[Induction of antitumor immune response in the mouse model after vaccination with B7.1 expressing tumor cells].

The aim of the study was the induction of an antitumor immune response by genetic modification of tumor cells. This was done by transfecting the costimulatory molecule B7.1 into a murine tumor cell line SCCVII/SF in order to increase T cell recognition and to install an immunologic memory. One cohort of immunocompetent mice C3 H/HeN were injected with B7.1 expressing tumor cells, while the control group received parental B7.1 negative tumor cells. In a second step those immunized mice were rechallenged by parental tumor cells and tumor growth was compared to a new control group. Transfection with B7.1 prohibits outgrowth of the SCCVII cell line. Animals that have been vaccinated in this way are partially immune towards a secondary exposition to B7.1 negative tumor cells. Outgrowth of this recurrent tumor is slowed down. Such an immunization builds up an immunologic memory. Vaccination with B7.1 expressing tumor cells lead to a partial protective tumor immunity in the SCCVII-C3 H/HeN mouse model.

Animals↗
PubMed1999

Assessment of the protection efficiency and comfort of personal protective equipment in real conditions of use.

The lack of scientific and technical knowledge in certain complex fields, together with schedule constraints, have lead to adopt in EN standards insufficiently validated tests, relying sometimes on an empirical approach. Thus, even personal protective equipment (PPE) with positive results in tests required by the standards can nevertheless prove to be unsatisfactory when used at work. Several research projects have already been carried out on equipment, fall arresting systems, protective clothing, and gloves by several health and safety institutes in Europe. The results would suggest practical solutions to improve the representativity of several European Committee for Standardization (CEN) test methods and to focus more on informing and training workers on the manner of wearing PPE, in particular respiratory protective equipment or hearing protectors.

Ergonomics↗
PubMed1999

Group theory used to improve the efficiency of transfer-matrix computations.

Transfer-matrix methodology is frequently used to deal with elastic scattering problems that require a solution of Schrödinger or homogeneous Maxwell equations in the continuous part of their spectra. As predicted by group theory, the basic states used for the expansion of the solutions can be separated into independent sets, thus enabling the scattering problem to be solved with a drastically improved efficiency. Depending on the peculiar symmetry in the problem, the basic states can present pairs of "conjugate sets," whose associated characters are complex conjugate of each other. When the potential energy takes strict real values, the transfer matrices corresponding to these conjugate sets have well-defined relationships that enable the transfer matrices of both conjugate sets to be computed from a single propagation step. This results in a further reduction of up to 50% of the total computation time. This paper presents the way group theory can be used systematically to improve the efficiency of transfer-matrix computations. In a first part, the basic states are separated into independent sets. Relationships between the transfer matrices corresponding to conjugate sets are then derived. The theory is finally illustrated by a simulation of electronic scattering by a C60 molecule in a projection configuration.

Journal Article↗
PubMed1999

The relationship between peripheral T cell reactivity to insulin, clinical remissions and cytokine production in type 1 (insulin-dependent) diabetes mellitus.

Antigenic proliferative responses of peripheral blood mononuclear cells (PBMC) to insulin were studied in 44 type 1 new-onset diabetic subjects. Of them, 14 (32%) had a stimulation index (> or =3) above the mean + 3 SD of 39 healthy controls and of 7 of 15 (47%) diabetic patients of long duration (P = 0.001). Responses to insulin were not dictated by specific major histocompatibility complex class II association and were not observed in normal subjects with diabetes-associated human leukocyte antigen-DR/DQ alleles. Whereas no relation of PBMC reactivity with insulin autoantibodies was found, there was a positive correlation with the presence of at least one of the four autoantibodies tested and with IA-2 antibody. An interesting finding was that the proportion of patients with subsequent low insulin requirement, up to 24 months, was significantly higher in patients who showed PBMC reactivity to insulin (8 of 8) than in those who did not (10 of 24, 42%; P = 0.004). The former had a higher mean stimulation index than the latter (3.3+/-2.6 vs. 1.5+/-0.6; P = 0.006). Furthermore, interleukin-4 (IL-4) production was lower in type 1 diabetic patients who proliferated to insulin than in those who did not (23+/-15 vs. 64+/-47 pg/mL; P = 0.04), but interferon-gamma, IL-2, and IL-10 productions were similar. In conclusion, these results suggest that proliferation to insulin may reflect the presence of an higher residual beta-cell mass.

Adolescent↗
PubMed1999

Effect of interferon alpha-2a on hormone receptor status in patients with advanced breast cancer.

The aim of this study was to assess the effect of recombinant interferon alpha-2a (rh-IFN) on estrogen (ER) and progesterone (PR) receptor expression in patients with advanced breast cancer and the evaluation of the effect of rh-IFN pretreatment on response to endocrine therapy with tamoxifen (TAM). Between June 1990 and November 1992, 20 patients with disseminated breast cancer and with metastatic skin nodules suitable for biopsy were entered into this study. Eighteen assessable patients underwent biopsy before and 2 weeks after treatment with rh-INF. rh-INF 3 x 10(6) IU were administered subcutaneously per day. Patients with ER expression at second biopsy were subsequently treated with 20 mg TAM daily. One patient had rapid disease progression and died before rebiopsy could be performed, and an additional patient refused second biopsy. All other patients were considered assessable. Thirteen patients showed ER expression before rh-IFN treatment, and 5 PR presented with expression. Rh-IFN increased ER expression in three patients and PR in four patients. No change was observed in 8 patients for ER and in 12 patients for PR. ER expression decreased in seven patients and PR expression decreased in two patients, respectively. Two patients showed a partial remission after subsequent treatment with TAM. Adverse reactions caused by rh-IFN were mainly flu-like symptoms. In this trial we found no systematic impact of rh-IFN on hormone receptor expression and, subsequently, on the response rate in patients with advanced breast cancer.

Adult↗
PubMed1998

Ca2+/calmodulin signals the completion of docking and triggers a late step of vacuole fusion.

The basic reaction mechanisms for membrane fusion in the trafficking of intracellular membranes and in exocytosis are probably identical. But in contrast to regulated exocytosis, intracellular fusion reactions are referred to as 'constitutive' as no final Ca2+-dependent triggering step has been observed. Although transport from the endoplasmic reticulum to the Golgi apparatus in the cell depends on Ca2+, as does endosome fusion and assembly of the nuclear envelope, it is unclear whether Ca2+ triggers these events. Membrane fusion involves several subreactions: priming, tethering and docking. Proteins that are needed for fusion include p115, SNAPs, NSF, SNAREs and small GTPases, which operate in these early reactions, but the machinery that catalyses the final mixing of biological membranes is still unknown. Here we show that Ca2+ is released from the vacuolar lumen following completion of the docking step. We have identified calmodulin as the putative Ca2+ sensor and as the first component required in the post-docking phase of vacuole fusion. Calmodulin binds tightly to vacuoles upon Ca2+ release. Unlike synaptotagmin or syncollin in exocytosis, calmodulin does not act as a fusion clamp but actively promotes bilayer mixing. Hence, activation of SNAREs is not sufficient to drive bilayer mixing between physiological membranes. We propose that Ca2+ control of the latest phase of membrane fusion may be a conserved feature, relevant not only for exocytosis, but also for intracellular, 'constitutive' fusion reactions. However, the origin of the Ca2+ signal, its receptor and its mode of processing differ.

Calcium↗
PubMed1998

[Hypotension in acyclovir therapy].

A 51 year old man developed Herpes zoster on the right arm (C5/C6) treated subsequently with aciclovir infusions (500 mg, 3/day). Ten months before hospital admission he did have a radical resection of a epi-oro-hypopharyngeal carcinoma (T4/N1/G2, M0; lymphangiosis carcinomatosa) as well as a partial laryngeal resection for a recurrence 3 months later and removal of a cervical lymph node metastasis after two further months. During aciclovir treatment the patient experienced repeated bradycardia with hypotension verifiable with the tilt-table test. The bradycardias could not be further characterized by ECC. Neither sonography nor CT-scans gave an indication for infiltration of the cervical course of the vagus or glossopharyngeal nerves. Serum catecholamines were, however, markedly reduced. After cessation of aciclovir the bradycardias and hypotensive episodes disappeared. A final tilt-table test was unremarkable. A reversible autonomic neuropathy induced by aciclovir seems a possible explanation.

Acyclovir↗